1. Field of the Invention
The present invention is directed to novel 2(5H)-furanones substituted in the 3 position with alpha hydroxy or alpha amino substituted alkyl or aralkyl groups, which compounds are active as anti-inflammatory agents. The present invention is also directed to pharmaceutical compositions which comprise one or more of the novel compounds of the invention, to the methods of using these pharmaceutical compositions, and to the chemical processes of making the novel compounds.
2. Brief Description of the Prior Art
Manoalide is a compound isolated from a marine sponge [E. D. de Silva et al., Tetrahedron Letters 21:1611-1614 (1980)] which has anti-inflammatory, immunosuppressive and analgesic properties. Manoalide (Compound 1) the structure of which is shown below, includes a 5-hydroxy-2(5H)-furanone moiety, attached in the 4-position of the furanone ring to the rest of the molecule. Certain analogs of manolide, such as seco-manoalide (Compound 2) dehydro-seco-manoalide (Compound 3) also have anti-inflamatory activity. For further description of the biological of manoalide and some of its derivatives reference is made to U.S. Pat. Nos. 4,447,445, 4,786,651, 4,789,749 and to European Patent Application No. 0 133 376 (published on Feb. 20, 1985). ##STR2##
Synthetic analogs of manoalide, particularly analogs having various substituents on the furanone moiety of manoalide, are described in several applications for United States Letters Patent by the same inventor as in the present application, the following of which have been allowed and are expected to issue as United States Letters Patent:
Ser. No. 259,225 filed on Oct. 18, 1988; PA0 Ser. No. 281,126 filed on Dec. 7, 1988. PA0 U.S. Pat. No. 4,855,320 discloses 5-arylalkyl-4-alkoxy-2(5H)-furanones as anti-convulsive and anti-epileptic agents. PA0 Chemical Abstracts Volume 107 236559t (1987) discloses 4-acyloxy 5-hydroxy-2(5H)-furanones. PA0 X is O, NH or NR.sub.1, where R.sub.1 is alkyl of 1 to 20 carbons or arylalkyl; PA0 Y is H, alkyl of 1 to 20 carbons, arylalkyl, aryl, substituted aryl, substituted arylalkyl, alkenyl containing one or more olephinic bonds, PO(OH).sub.2, PO(OH)OR.sub.2, PO(OH)R.sub.2 PO(OR.sub.2).sub.2, where R.sub.2 is independently alkyl of 1 to 20 carbons, phenyl, or substituted phenyl, further Y is CO--R.sub.3, CO--OR.sub.3, CONHR.sub.3, SO.sub.2 R.sub.3, SO.sub.2 NHR.sub.3, (CH.sub.2).sub.n --O--R.sub.3, or (CH.sub.2).sub.n --O--(CH.sub.2).sub.m --O--R.sub.3, where n, and m, are integers and are independently 1 to 20 and R.sub.3 is H, alkyl, alkenyl containing one or more olephinic bonds, aryl, substituted aryl, arylalkyl or substituted arylalkyl, with the proviso that when Y is CO--R.sub.3, CO--OR.sub.3, and CONHR.sub.3 then R.sub.3 is not hydrogen.
Published European Patent Application No. 0 295 056 discloses 4-substituted 5-hydroxy-2(5H)-furanones having anti-inflammatory, immunosuppressive and anti-proliferative activity where the substituents in the 4 position are a variety 1-hydroxyalkyl, 1-acyloxy-alkyl and 1-carbamoyloxy-alkyl groups.
Published European Patent Application No. 0 209 274 discloses 4-alkyl-5-hydroxy-2(5H)-furanones as anti-inflammatory and anti-allergy agents.